1. Field of the Invention
This invention generally relates to an apparatus and method for performing a variety of chemical and physical operations upon a small sample of fluid or fluid-like material. In particular, the invention is directed to a thin, flat, hollow test strip the interior of which is filled with an inert liquid medium and which includes at least one physical, chemical, biological or detecting station wherein a blister of sample may be introduced into the top of said strip and positively propelled forwardly ahead of a pinch line through the inert liquid medium to each station.
2. Description of the Prior Art
In a typical continuous flow type analyzer samples of fluids to be analyzed are pumped sequentially through a long "pipe" or column and at various points along the pipe are subjected to specific chemical or physical processes. Often the individual samples are broken up by air bubbles in the pipe into small segments. Each segment receives the same treatment and at the end of the pipe the segments are typically comingled or enter another type of analyzer, for example, a colorimeter. In operation, different samples of materials to be analyzed are often separated one from another by a slug of water. Continuous flow analyzers of the type just described are produced by the Technicon Corporation and are well known to those of ordinary skill in the art. While such continuous flow analyzers can be very effective and do accomplish their desired goal, they do possess several drawbacks. Chief among the drawbacks encountered with such continuous flow type analyzers is that they are generally expensive, bulky in size, and non-disposable. Conversely, the subject of this invention is a flexible analytical type strip which will allow relatively complicated chemical processes to take place therein but which does not require sophisticated expertise to operate. Furthermore, the flexible analytical strip of this invention is much less expensive to produce and may be easily disposed of after use. Alternatively, however, it may be possible to re-charge the tube if so desired.
In general, the encapsulation of a reagent in plastic is not entirely new. For instance, part of the technique employed by the well known Polaroid Land Camera is to capture a chemical reagent in a plastic pouch and then, by applying roller pressure to it, force the pouch to rupture and spread its contents over a sheet of chemically treated paper for the purpose of developing the same. Also, the desalination of salt water has been accomplished in emergencies by introducing the sea water into a pouch containing a reactive silver containing substance and then squeezing the water out through a filtering medium into the mouth.
Prepackaged plastic analyzers are described in several recent United States patents, of which the following may be significant with respect to the instant invention: Johnson et al U.S. Pat. No. 3,476,515; Blackburn et al. U.S. Pat. No. 3,476,515; Johnston et al. U.S. Pat. No. 3,554,704; Schwartz U.S. Pat. No. 3,660,033; Agnew et al. U.S. Pat. No. 3,689,224; Goldstein et al. U.S. Pat. No. 3,697,227; Shapiro U.S. Pat. No. 3,713,780 and Nighohossian et al. U.S. Pat. No. 3,715,189. The foregoing can be broadly described as being plastic devices containing one or more reaction chambers into which certain chemical agents or samples may be added. In Johnson et al the agents are added by rupturing an internal depression filled with reagent. In Schwartz, the reagent or indicator is located in the reaction chamber itself. Guigan et al. U.S. Pat. No. 3,620,678; Fetter, U.S. Pat. No. 3,552,928 and Sirago et al. U.S. Pat. No. 3,713,779 are also indicative of prior art manipulative laboratory devices.
Of special interest is Forestiere, U.S. Pat. No. 3,036,894. The Forestiere patent discloses a "Method of Using Testing Containers" in which a linear chain of small, joined plastic reaction vessels, which are hollow chambers or pouches or bags containing predetermined amounts of reagents are connected together between two pieces of plastic material in strip form. A sample of material is introduced into the top hollow chamber and then squashed through the subsequent chambers in linear order by means of a pair of squeeze rollers. The reagents in the respective hollow chambers are separated one from another by an adhesive barrier "of relatively small area" which will break open when the matters in the chambers are squeezed strongly against it.
The present invention differs from the device disclosed in the Forestiere patent in several major respects. Most importantly, the present invention has nothing to do with hollow containers, chambers, pouches or bags. According to the Forestiere disclosure reactions are constrained to a pre-set, linear order. That is the sample, after being put in the top bag, is constrained to enter into the following chamber and react with the reagent there and then must enter into the next chamber, and so on in predetermined order. In the present invention the direction of blister travel can be changed according to the demands of the experiment. The device disclosed in U.S. Pat. No. 3,036,894 can be unsatisfactory in operation as may be seen from the following consideration. Upon crushing or squashing the entrance chamber the sample is squeezed into the first hollow reaction chamber and then reacts with the reagent therein. The entire contents of the first reaction chamber is then crushed into the second pouch to react with the reagent there. The combined contents of the first and second pouches are then squeezed into the third and so on. This may cause the adhesive barriers down the chain to expand open far in advance of the sample being squashed through the chain of chambers and cause the final chamber which is sealed at its end to distend and balloon. The effect may have to be mitigated by having compressible reagents or having the chambers largely filled with air. To prevent excessive ballooning appropriate venting mechanics would have to be provided. However, vents would largely militate against the processing of noxious material or virulent bacteria, viruses, etc. The device according to U.S. Pat. No. 3,036,894 involves not only chambers in a fixed linear array but also predetermined amounts of reagent in fixed positions with which to react the sample. In the present invention the reagents of interest may be in fixed position and be of predetermined amount but may also be in any position desired, even mobile of themselves and of any desired amount because in the present invention a blister may be not only of the material being tested but a second (or third, or fourth, etc.) blister may be a blister containing the reagent. Such a reagent blister may be pushed around, separated into portions, etc. at the will of the experimenter.
In none of the foregoing well known devices does the analysis appear to be performed in an apparatus or according to the method of the present invention. Among the chief differences is the fact that, due to the unique construction of the present invention, it is possible to manipulate the "blister" of sample through a plurality of physical and chemical operation stations in a manner not previously described by the prior art. By keeping the sample in a discrete blister it is possible to perform the analysis with little loss of volume due to sidewall adhesion effects and with minimum mixing with atmospheric air. This allows for relatively precise volumetric analysis and a great deal of physical control over the sample. Also it is possible to overcome surface tension problems associated with small specimen sizes, therefore improving accuracy with smaller samples. In general, gravity has not been found to be satisfactory as a driving mechanism because it is not strong enough to overcome the resistance associated with inert liquid medium. However, the present invention also contemplates the use of apparatus and techniques to accomplish the propulsion of the discrete blister down a strip. Obviously, many more operations can be performed on a blister since it loses little of its volume as it is analyzed. In this respect, much more sophistocated analysis can be performed on the sample than would be previously done without the aid of very expensive equipment. It was in the context of such a need that the following apparatus and method was invented.